Natural product discovery from marine-derived microorganisms and the investigation of metabolomic changes from in-situ fermentations of marine-derived Actinomycetota

Marine microorganisms are well known for their unique and bioactive natural products and are thought to be the “true” source of many invertebrate-derived compounds.However, many natural products remain silent, locked behind transcriptional and translational regulation when grown under standard laboratory methods. This thesis describes two studies that use untargeted metabolomics as an approach for natural product discovery. The first study focused on a media study of 20 marine-derived bacteria with prior observed biological activity. Metabolomics and cross-referencing molecular weight with online databases assisted in prioritizing the discovery of a new sesterterpene from a coral-derived Streptomyces sp., guanahanolide A(13). Guanahanolide A(13) contains an unprecedented perhydrophenalene sesterterpene skeleton and showed moderate cytotoxicity against human cancer cell lines MCF-7, HTB-26, and HCT-116. The second study implemented an in-situ fermentation within seawater, sediment, and a sponge in San Salvador Island, Bahamas. Mangrove fermentations containing sediment-derived Streptomyces sp. was found to increased natural product production when “incubated” in seawater compared to sediment. Whereas the sponge-derived Streptomyces sp. was observed to potentially increase natural product production when “incubated” in a giant barrel sponge, compared to seawater or sediment. In conclusion, this thesis provides evidence to support the notion that marine microorganisms remain an underexplored source of new chemistry and accentuates the knowledge gap in chemical ecology of marine microorganisms